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Plasma Neurofilament Light Chain Is Associated with Poor Functional Outcome and Mortality Rate After Spontaneous Subarachnoid Hemorrhage

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Abstract

The initial clinical status after subarachnoid hemorrhage (SAH) is an important outcome predictor, but the mechanisms behind the early brain injury (EBI) remains incompletely understood. Elevated neurofilament levels in the cerebrospinal fluid at protracted stages after SAH are associated with poor outcome, but the potential association between plasma neurofilament (pNfL) levels during EBI, disease severity on admission, and poor outcome remains unaddressed. Plasma NfL (pNfL) was measured by single molecule array in 44 SAH patients on admission and 24 h after ictus, as well as in 44 controls. Disease severity on admission was assessed by validated scoring systems, and day 30 modified Rankin Scale (mRS) score was registered. Admission levels of pNfL correlated with clinical disease severity scores (rho = 0.43, p < 0.01 and rho = 0.48, p < 0.001) as well as day 30 mRS score (rho = 0.53, p < 0.001). Each quartile increase in pNfL was independently associated with poor functional status (mRS > 4) [odds ratio = 1.98, 95% confidence interval (CI): 1.01–3.88, p = 0.05]. Non-survivors had higher pNfL than survivors; on admission [17.6 pg/mL (IQR 11.4) vs. 8.4 pg/mL (IQR: 8.9), p < 0.01] and 24 h after ictus [29.9 pg/mL (IQR 90.4) vs 7.8 pg/mL (IQR 26.9), p = 0.01]. Each quartile increase in pNfL was independently associated with reduced survival rate [log-rank = 0.02, hazard ratio = 2.29 (95% CI): 1.15–4.57), p = 0.02]. PNfL levels are associated with disease severity during the EBI phase of SAH. Higher pNfL levels during EBI are associated with poor functional outcome on day 30 after ictus and increased mortality rate.

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Contributors

CVBH, AMH, and TP contributed to the conception and design of the study. CVBH, TG, SVL, NS, AMH, and TP contributed to the acquisition and analysis of data. All authors drafted/revised the manuscript for its intellectual content, approved the final version, and agreed to be accountable for all aspects of the work.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark

    Claus Vinter Bodker Hviid, Tua Gyldenholm, Tina Parkner & Anne-Mette Hvas

  2. Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark

    Signe Voigt Lauridsen

  3. Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark

    Niels Sunde

  4. Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark

    Niels Sunde, Tina Parkner & Anne-Mette Hvas

Authors
  1. Claus Vinter Bodker Hviid
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  2. Signe Voigt Lauridsen
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  3. Tua Gyldenholm
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  4. Niels Sunde
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  5. Tina Parkner
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  6. Anne-Mette Hvas
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Correspondence to Claus Vinter Bodker Hviid.

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Funding Information

The study was funded by “Laege Sofus Carl Emil Friis og Hustru Olga Doris Friis Legat”; “Grosserer L.F. Foghts Foundation (grant number 21.342),” and the AP Moller Foundation (grant number 17-L0027). CVBH received a scholarship from the Health Research Fund of Central Denmark Region.

Conflict of Interest

None of the authors have any conflicts of interest regarding the present paper but have the following general conflicts of interest: Anne-Mette Hvas has received a speaker’s fee from Astellas, CSL Behring, Bayer, Bristol-Myers Squibb, and Leo Pharma and unrestricted research support from Octapharma, CSL Behring, and Leo Pharma.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

The study was approved by the Regional Ethical Committee of Central Denmark Region (1–10–72-95-14, version 7, 02102017 and 1–10–72-94-14, version 7, 05102017) and the National Data Protection Agency (1–16–02-225-14 and 1–16–02-224-14).

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Written informed consent was obtained from all individual participants included in the study or from their legal representative.

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Hviid, C.V.B., Lauridsen, S.V., Gyldenholm, T. et al. Plasma Neurofilament Light Chain Is Associated with Poor Functional Outcome and Mortality Rate After Spontaneous Subarachnoid Hemorrhage. Transl. Stroke Res. 11, 671–677 (2020). https://doi.org/10.1007/s12975-019-00761-4

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  • DOI: https://doi.org/10.1007/s12975-019-00761-4

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